1. Field of the Invention
The present invention relates to the use of a dietary fiber, particularly a fructan, for the manufacture of a composition for preventing and/or inhibiting the systemic growth of pathogenic bacteria in humans and vertebrates. The present invention also relates to a method for inhibiting the systemic growth of pathogenic bacteria in humans and vertebrates by administration of a composition containing a dietary fiber, particularly a fructan.
2. Background and Prior Art
Dietary fiber is a general term that is used to describe food ingredients that are resistant to hydrolysis by the digestive secretions of humans and vertebrates (referred to in short herein by the term resistant). Historically, dietary fibers have been considered to primarily consist of lignin, cellulose, hemicellulose or pectin. However, recent interest has focused on other dietary fibers such as, e.g., resistant starch and resistant fructans, including levan, inulin and oligosaccharides.
The sources of dietary fiber vary widely and may include trees (cellulose), beet pulp from sugar beets, and extracts from plants, plant parts and fruits (e.g., gum arabic, fructans including levan from Phleum pratense, and inulin and fructo-oligosaccharide, also named oligofructose, from roots of chicory and from tubers of Dahlia and Jerusalem artichoke; citrus pectin from fruits; carrageenan from seaweed; and husks from nuts (e.g., peanut hulls). Although resistant oligosaccharides have traditionally not been considered as dietary fibers, they do meet the necessary criteria, and are now generally accepted as such. Resistant oligosaccharides and polysaccharides can also originate from bacterial activity (e.g., fructo-oligosaccharide, levan and inulin) and can also be obtained by enzymatic synthesis, e.g., fructo-oligosaccharide from sucrose. Resistant oligosaccharides can be obtained too by partial hydrolysis of resistant polysaccharides, for example fructo-oligosaccharide by partial, acidic or enzymatic hydrolysis of fructans. The terms fructo-oligosaccharide and oligofructose are used herein interchangeably.
Fructans, i.e., levan, inulin and oligofructose, commonly occur as a polydisperse mixture of chains of carbohydrates which consist mostly of fructose units and in which fructosyl-fructose linkages constitute the majority of the linkages. Fructo-oligosaccharide or oligofructose, which is in fact a fructan composed of molecules with less than 10 saccharide units, can be obtained by extraction from plant material, by partial hydrolysis, either acidic hydrolysis or enzymatic hydrolysis, of fructans, particularly inulin, as well as by enzymatic synthesis from sucrose. All these types of fructans are embraced herein by the term fructan.
Fructans, including levan, inulin and oligofructose, are well known in the art and are considered as dietary fibers. Levan consists of chains of fructose units which are mostly or exclusively connected to each other by β(2-6) linkages. A terminal glucose unit may be present or not. Inulin consists of chains of fructose units which are mostly or exclusively connected to each other by β(2-1) linkages. Most of the inulin chains terminate in one glucose unit but the presence of said glucose unit is not necessary. Levan mostly occurs as branched fructose chains, whereas inulin is composed of linear chains of fructose units but it may also occur as chains of fructose units which are branched to a larger or lesser extent. All said fructans, i.e., levan, inulin and oligofructose, are suitable in the present invention.
Inulin occurs at concentrations of about 10 to 20% on fresh weight in chicory, dahlia tubers and Jerusalem artichoke, from which it can be isolated at industrial scale, purified, and optionally refined to remove impurities and undesired fractions of carbohydrates, according to known techniques.
Inulin can be represented by the general formulae GFn and Fm, wherein G represents a glucose unit, F represents a fructose unit, n represents the number of fructose units linked to the terminal glucose unit, and m represents the number of fructose units linked to each other in the carbohydrate chain. The number of saccharide units (fructose and glucose units) in one fructan molecule, i.e., the values n+1 and m in the above formulae, are commonly referred to as the degree of polymerisation, represented as (DP). A further feature of inulin is the (number) average degree of polymerisation, represented by (DP), which is the mean number of saccharide units per polysaccharide (inulin) molecule.
Inulin from chicory is commercially available as RAFTILINE® from ORAFTI, (Tienen, Belgium), in various grades such as, for example, ST (which has a (DP) of about 10 and contains in total about 8% by weight glucose, fructose and sucrose), LS (which has a (DP) of about 10 but which contains in total less than 1% by weight glucose, fructose and sucrose), and HP (which has a (DP) of ≦23, commonly of about 25, and contains in total less than 1% by weight of glucose, fructose and sucrose).
Fructo-oligosaccharide (oligofructose) consists of chains of less than 10 fructose units which are mostly or exclusively connected to each other by β(2-6) linkages or β(2-1) linkages, and a terminal glucose unit may be present.
Oligofructose is commercially available, for example as RAFTILOSE® from ORAFTI, (Tienen, Belgium), in various grades such as, for example, RAFTILOSE® P95 which contains about 95% by weight oligofructose, composed of chains with a degree of polymerisation ranging from 2 to about 7, typically with a (DP) of 3.5 to 4.5, and containing about 5% by weight in total of glucose, fructose and sucrose.
Dietary fibers can be classified based on their solubility in water and can also be classified on whether or not the dietary fiber can be used as an energy source by bacteria of the gastro-intestinal tract whereby the dietary fiber is metabolised (fermented). Fibers that can be used by gastro-intestinal bacteria are considered to be fermentable. The terms fermentable fibers and dietary fibers are used interchangeably herein.
Dietary fibers appear to have relevance in improving human and animal health. The gastro-intestinal tract of humans and vertebrates contains many species of bacteria, some of which that are commonly present are considered as beneficial, whereas others, which typically are present in the gastro-intestinal tract in case of a bacterial infection, are considered as pathogens. The term pathogenic bacteria includes herein typically pathogenic bacteria as well as putrefactive bacteria.
Beneficial bacteria include the abilities of the production of lactic acid, other short chain fatty acids, metabolites and other chemical compounds, that are known to have beneficial effects on certain bodily functions and that suppress the growth of pathogenic bacteria species in the gastro-intestinal tract, a process called inhibition. Promotion of the growth of said beneficial bacteria, such as bifidobacteria and lactobacilli, by intake of dietary fibers, particularly inulin and resistant oligosaccharides such as, e.g., oligofructose, thus results in various beneficial effects for the host, including increase of stool weight and stool frequency with reduction of constipation, reducing effects of glycemic response, effects on blood cholesterol and on HDL/LDL ratio, and effects on serum lipids. Further effects include immuno-modulating effects resulting i.a. in protective, inhibitive and/or curative effects on cancer, particularly on breast and on colon cancer. Beneficial bacteria of the gastro-intestinal tract typically include bacteria of the genus Bifidobacterium (Bifidus) and Lactobacillus. 
Pathogenic bacteria may cause to the host various diseases and dysfunctions, including diarrhoea and infectious disease, such as entero-colitis, gastro-intestinal ulcers and Crohn's disease.
It is known that beneficial bacteria, particularly those of the genus Bifidobacterium and Lactobacillus, have the capacity to ferment dietary fibers, typically fructans and resistant oligosaccharides, more effectively than pathogenic intestinal bacteria. Thus, the intake of dietary fibers, particularly of fructans and/or resistant oligosaccharides, increases the density of lactic acid producing bacteria in the gastro-intestinal tract and reduces the number of undesirable Enterobacteriaceae. The latter include most pathogens such as, e.g., bacteria of the genus Clostridia, Bacteroides, Listeria, Candida and Salmonella. Accordingly, intake of dietary fibers such as fructans and/or oligofructose can be used to selectively stimulate the growth of beneficial bacteria in the gastro-intestinal tract. The improvement of the ratio beneficial/pathogenic bacteria in turn results in beneficial health effects for the host.
To prevent, control and/or remedy disorders and diseases of the gastro-intestinal tract of humans and vertebrates caused directly or indirectly by pathogenic bacteria, several approaches are used today. A first approach is the intake of antibiotics which can selectively remove a target genus of bacteria. A second approach is the intake of probiotics, which are viable, beneficial bacteria, such as bifidobacteria and lactobacilli, enabling to alter the composition and, accordingly, the metabolism of the gastro-intestinal flora, and thus to beneficially affect the host's health. A third approach involves the intake of prebiotics, i.e., dietary fibers, which increases the ratio of beneficial/pathogenic bacteria in the gastro-intestinal tract with a concurrent reduction of undesired, pathogenic and putrefactive bacteria, resulting in beneficial health effects for the host, such as, e.g., permitting faster recovery of mucosal mass and digestive capacities, and the inhibition and/or relief of gastrointestinal dysfunctions and diseases. In a fourth approach, lectins, certain monosaccharides such as, e.g., mannose, and certain organic acids such as mono-, di- and tricarboxylic acids, have also been used to selectively decrease the density of some pathogenic bacteria.
Gastro-intestinal dysfunctions and diseases, such as severe diarrhoea and gastro-enteritis often lead to disruption of the mucosal barrier which increases the risk of translocation of bacteria from the gastro-intestinal tract to the mesenteric lymph nodes and to the blood stream, often causing subsequent sepsis in the host.
Nowadays, said subsequent sepsis is commonly inhibited and treated by means of antibiotics which are administered to the infected host. Besides, in order to control the growth of pathogenic bacteria and infection of the gastro-intestinal tract, as well as to prevent subsequent systemic infection by said pathogenic bacteria in vertebrates, often antibiotics are added to feed.
However, there is a growing concern about the use of antibiotics because of the development of bacterial strains that are resistant to antibiotics and the potential impact they have on the environment. Another detriment of the treatment with some antibiotics is the disruption of the normal gastro-intestinal bacterial flora.
Accordingly, there is an ongoing search for compounds and methods for the prevention, inhibition and treatment of systemic bacterial infections which are free of one or more disadvantages presented by the compounds and methods which are currently used in this respect.